The proposed research program is designed to study the interaction between the hypothalamus, the pituitary, and the ovaries in the regulation of gonadotropin and prolactin secretion. To accomplish this aim, the concentration and turnover of several CNS neuromediators will be studied, including the catecholamines, prostaglandins, serotonin, catechol estrogens, and TRF. Quantitative data so obtained will be correlated with levels of LRF in the hypothalmus and circulating gonadotropins, prolactin and steroids. This method of analysis will be applied to female rats at frequent intervals during the estrous cycle and in the various stages of reproductive senescence. The response to castration and the effects of steroid administration will also be investigated. These studies should provide critical information on the steady-state activity of catecholamines and other neuromediators under defined reproductive environments. In order to examine the minute-to-minute output of CNS neuromediators, the sheep will be used as a model. In the sheep the estrous cycle, anestrus, and the seasonal transitions between the two will be studied. This will be done by frequent sampling of cephalic blood and ventricular CSF in ewes fitted with jugular-carotid catheters and "push-pull" cannulae. Studies in the sheep should provide detailed information on the dynamic pattern of neuromediator output in the conscious animal. Catecholamines, catecholamine metabolites, catechol estrogens, and serotonin will be quantified by radioenzymatic assay. Prostaglandins, LRF, TRF, pituitary and steroid hormones will be measured by radioimmunoassay. Tissue from hypothalamic regions will be obtained by microdissection. The proposed research should provide significant insights into the neuroendocrine regulation of gonadotropin and prolactin secretion. These insights should suggest approaches to fertility control and the management of reproductive disorders.